Using Nevirapine to Prevent Mother-to-Child HIV Transmission During Breastfeeding

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ClinicalTrials.gov Identifier: NCT00074412

Recruitment Status :
Completed

First Posted : December 15, 2003

Results First Posted : September 16, 2013

Last Update Posted : September 16, 2013

Sponsor:

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators:

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

The many benefits of breastfeeding are well documented. However, because of the risk of mother-to-child transmission (MTCT) of HIV from an HIV infected mother to her infant, there is considerable concern over the practice, especially in developing countries. The purpose of this study is to determine the safety and effectiveness of the anti-HIV drug nevirapine (NVP) in preventing MTCT of HIV in breastfeeding infants born to HIV infected women in South Africa, Tanzania, Uganda, and Zimbabwe.

Condition or disease

Intervention/treatment

Phase

HIV Infections

Drug: NevirapineDrug: Nevirapine placebo

Phase 3

Detailed Description:

Breastfeeding provides general health, growth, and development benefits to an infant and significantly decreases the risk of certain acute and chronic diseases. Breastfeeding also decreases financial burden on the mother by decreasing the need for infant formula and health care for the infant. However, clinical evidence has shown that HIV can be readily transmitted through breast milk, although the risk of HIV MTCT over time while breastfeeding has been difficult to determine. Given the many advantages of breastfeeding and the significant obstacles to substituting formula for breast milk in developing countries, there is an urgent need to make breastfeeding by HIV infected women safe. This study will evaluate the safety and efficacy of an extended NVP regimen for prevention of MTCT of HIV through breastfeeding.

This study will last approximately 3.5 years. Mother/infant pairs will be enrolled over a period of 18 to 24 months. During the third trimester of pregnancy, HIV infected participants will receive HIV counseling and the intrapartum/neonatal two-dose NVP prophylaxis regimen to prevent MTCT. Mothers will also be given infant feeding options counseling and information on administering the study drug to the infant. Infants who were randomly assigned to receive a placebo and older than 6 weeks of age as of 08/10/07 OR to receive NVP will continue their treatment assignment. Infants who were randomly assigned to receive a placebo and are 6 weeks of age or less as of 08/10/07 will receive open-label NVP through Day 42 of life. For all other participants, all randomized infants will receive extended NVP through 6 weeks (Day 42) of life. All eligible infants will be randomly assigned to one of two groups at Week 6 following birth. The first group will receive extended NVP treatment; the second group will receive nevirapine placebo. Randomized infants will receive the extended NVP or NVP placebo through the first 6 months of life or until cessation of breastfeeding, whichever occurs earlier. Mothers will be instructed to begin giving their infants their assigned intervention starting at Day 3 to Day 7 postpartum. All mothers and infants outside of the study will be offered the local standard of care antiretroviral (ARV) regimen for the prevention of MTCT, but these ARVs will not be provided by the study.

Follow-up evaluations will be conducted at Weeks 2 and 6 and Months 3, 6, 12, and 18 for mothers, and at Weeks 2, 5, 6, and 8 and Months 3, 4, 5, 6, 9, 12, and 18 for infants. Study visits will include physical examinations, blood tests (including HIV tests), and medical histories. Study participants will be followed for up to 3.5 years.

For those infants who were randomized at 6 weeks and who initiated study drug we looked at the frequency and severity of adverse reactions through 18 months of study. The severity of all AEs was graded according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events. The term severity is described as the intensity grade or level for specific event (i.e. mild, moderate, severe, or life-threatening). Severity is not the same as seriousness.

Secondary Outcome Measures :

Proportion of Infants Who Are Alive and HIV-uninfected in the Two Arms [ Time Frame: At Months 6 and 18 ]

Relative Rates of HIV Infection in the Two Arms [ Time Frame: At Month 18 ]

Infant Survival Rates (Mortality Regardless of HIV Infection) in the Two Arms [ Time Frame: At Month 18 ]

Frequency and Duration of Maternal Plasma and Breast Milk NVP-resistant HIV Strains and the Relationship With HIV Transmission [ Time Frame: Throughout study ]

Relationship Between Maternal Plasma and Breast Milk RNA Levels and the Risk of MTCT [ Time Frame: Throughout study ]

Frequency and Duration of NVP-resistant HIV Strains in Plasma of HIV-infected Infants [ Time Frame: Throughout study ]

Rates of Disease Progression as Defined by CD4 Counts, HIV-1 RNA PCR, and Mortality in Infected Infants in the Two Arms [ Time Frame: Throughout study ]

NVP Concentrations in Infants Determined to be HIV-infected and in a Sample of HIV-uninfected Infants [ Time Frame: Week 8 and Month 3 ]

Samples for NVP concentration were selected from the Version 3.0 infants who were randomized to NVP at 6 weeks and whose mothers were not on 3 or more antiretrovirals at the time of randomization. All infants HIV-infected by 6 months who met this criteria were selected and matched to HIV-uninfected infants who also met this criteria in a 1:3 ratio. NVP concentrations were measured by high liquid chromatographic/mass spectroscopy from the aforementioned infants plasma samples collected at week 8 and month 3. Median NVP concentrations were compared

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Ages Eligible for Study:

Child, Adult, Senior

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Note: As of 08/10/07, the arm assignments for current and new participants have changed. Please see the above description for this trial for more information.

Inclusion Criteria for Mothers:

18 years of age or older

HIV infected

In third trimester of pregnancy, or at most 3 days post-delivery

If baby is not yet born, planning to deliver at a facility where the study is being conducted

Plan to breastfeed

Exclusion Criteria for Mothers:

Complications with this pregnancy

Serious medical condition that would interfere with the study (e.g., that would prevent breastfeeding or adherence to the follow-up schedule), as judged by the on-site clinician

Inclusion Criteria for Infants:

Born to an HIV infected mother who is eligible for the study

Weighed at least 2000 grams (4.4 lbs) at birth

Blood sample obtained from the infant for HIV-1 DNA PCR, CBC with differential, and ALT

Infants in a multiple birth are eligible only if both/all infants are eligible for the study and assigned to the same study group

Able to breastfeed (e.g., mother and infant alive with no condition apparent that would prevent breastfeeding)